A combined score of clinical factors and serum proteins can predict time to recurrence in high grade serous ovarian cancer

Mysona, David; Pyrzak, Adam; Purohit, Sharad; Zhi, Wenbo; Sharma, Ashok; Tran, Lynn; Tran, Paul; Bai, Shan; Rungruang, Bunja; Ghamande, Sharad; She, Jin Xiong

doi:10.1016/j.ygyno.2018.12.015

Cited by 27 publications

(23 citation statements)

References 22 publications

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“…The authors identified BDNF (brain derived neurotrophic factor) and PDGF (Platelet Derived Growth Factor) molecules as strong predictors of progression-free survival. PDGFA is also present in the PEA panel used in our study and was found to be upregulated in OC-plasma, complementing the observation of Mysona and colleagues (44).…”

Section: Discussionsupporting

confidence: 90%

“…A SOMAscan-based analysis of ovarian HGSC serum samples was published very recently, but this work was carried out with a different goal than our study, namely the identification of prognostic biomarkers (44). The authors identified BDNF (brain derived neurotrophic factor) and PDGF (Platelet Derived Growth Factor) molecules as strong predictors of progression-free survival.…”

Section: Discussionmentioning

confidence: 99%

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Multi-platform Affinity Proteomics Identify Proteins Linked to Metastasis and Immune Suppression in Ovarian Cancer Plasma

Graumann

Finkernagel²,

Reinartz³

et al. 2019

Front. Oncol.

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A central reason behind the poor clinical outcome of patients with high-grade serous carcinoma (HGSC) of the ovary is the difficulty in reliably detecting early occurrence or recurrence of this malignancy. Biomarkers that provide reliable diagnosis of this disease are therefore urgently needed. Systematic proteomic methods that identify HGSC-associated molecules may provide such biomarkers. We applied the antibody-based proximity extension assay (PEA) platform (Olink) for the identification of proteins that are upregulated in the plasma of OC patients. Using binders targeting 368 different plasma proteins, we compared 20 plasma samples from HGSC patients (OC-plasma) with 20 plasma samples from individuals with non-malignant gynecologic disorders (N-plasma). We identified 176 proteins with significantly higher levels in OC-plasma compared to N-plasma by PEA (p < 0.05 by U-test; Benjamini-Hochberg corrected), which are mainly implicated in immune regulation and metastasis-associated processes, such as matrix remodeling, adhesion, migration and proliferation. A number of these proteins have not been reported in previous studies, such as BCAM, CDH6, DDR1, N2DL-2 (ULBP2), SPINT2, and WISP-1 (CCN4). Of these SPINT2, a protease inhibitor mainly derived from tumor cells within the HGSC microenvironment, showed the highest significance (p < 2 × 10−7) similar to the previously described IL-6 and PVRL4 (NECTIN4) proteins. Results were validated by means of the aptamer-based 1.3 k SOMAscan proteomic platform, which revealed a high inter-platform correlation with a median Spearman ρ of 0.62. Likewise, ELISA confirmed the PEA data for 10 out of 12 proteins analyzed, including SPINT2. These findings suggest that in contrast to other entities SPINT2 does not act as a tumor suppressor in HGSC. This is supported by data from the PRECOG and KM-Plotter meta-analysis databases, which point to a tumor-type-specific inverse association of SPINT2 gene expression with survival. Our data also demonstrate that both the PEA and SOMAscan affinity proteomics platforms bear considerable potential for the unbiased discovery of novel disease-associated biomarkers.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Multi-platform Affinity Proteomics Identify Proteins Linked to Metastasis and Immune Suppression in Ovarian Cancer Plasma

Graumann

Finkernagel²,

Reinartz³

et al. 2019

Front. Oncol.

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“…By using SOMAScan, they verified that APOA1, CGB, FSHB, IL-6, MMP7 could be used as potential diagnostic biomarkers in OC (Graumann et al, 2019). In another study, Mysona et al (2019) used SOMAScan to continuously exam 1129 proteins in the blood of patients with OC. Twenty six proteins verified by Luminex test had a positive correlation with OC recurrence, like BDNF, MDC, PAI1, PDGF, and so on (Mysona et al, 2019).…”

Section: Cancersmentioning

confidence: 97%

“…In another study, Mysona et al (2019) used SOMAScan to continuously exam 1129 proteins in the blood of patients with OC. Twenty six proteins verified by Luminex test had a positive correlation with OC recurrence, like BDNF, MDC, PAI1, PDGF, and so on (Mysona et al, 2019). Their works are meaningful for predicting the prognosis of OC patients after treatment remission, and are expected to provide early intervention and consolidation treatment for patients who may relapse.…”

Section: Cancersmentioning

confidence: 99%

Advances in Aptamer-Based Biomarker Discovery

Huang

Chen

et al. 2021

Front. Cell Dev. Biol.

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The discovery and identification of biomarkers promote the rational and fast development of medical diagnosis and therapeutics. Clinically, the application of ideal biomarkers still is limited due to the suboptimal technology in biomarker discovery. Aptamers are single-stranded deoxyribonucleic acid or ribonucleic acid molecules and can selectively bind to varied targets with high affinity and specificity. Compared with antibody, aptamers have desirable advantages, such as flexible design, easy synthesis and convenient modification with different functional groups. Currently, different aptamer-based technologies have been developed to facilitate biomarker discovery, especially CELL-SELEX and SOMAScan technology. CELL-SELEX technology is mainly used to identify cell membrane surface biomarkers of various cells. SOMAScan technology is an unbiased biomarker detection method that can analyze numerous and even thousands of proteins in complex biological samples at the same time. It has now become a large-scale multi-protein biomarker discovery platform. In this review, we introduce the aptamer-based biomarker discovery technologies, and summarize and highlight the discovered emerging biomarkers recently in several diseases.

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“…The clinical utility of circulating concentrations of BDNF have been explored in neuropsychiatric disorders such as obsessive compulsive disorder 4 , eating disorders 5 , depression 6 – 9 , schizophrenia 10 , bipolar disorder 9 , 11 , 12 , as well as neurodegenerative diseases including Parkinson’s, Huntington’s, and Alzheimer’s disease 13 , 14 . Furthermore, increased circulating BDNF concentrations relative to controls have been linked with several different cancers 15 – 17 and gynecological disorders including polycystic ovarian syndrome 18 and endometriosis 19 – 21 . Indeed, women with endometriosis have elevated circulating BDNF concentrations compared to women without disease 19 – 21 , which correlated with pelvic pain 21 , and decreased after surgical removal of lesions 19 .…”

Section: Introductionmentioning

confidence: 99%

Factors affecting stability of plasma brain-derived neurotrophic factor

Wessels

Agarwal

Somani

et al. 2020

Sci Rep

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Circulating concentrations of brain-derived neurotrophic factor (BDNF) have been linked to cancer, neuropsychiatric, diabetes, and gynecological disorders. However, factors influencing plasma storage and subsequent BDNF quantification are incompletely understood. Therefore, the anticoagulant used in plasma separator tubes, storage-time, storage-temperature, and repeated freeze–thaw cycles on circulating BDNF concentrations was evaluated. Peripheral blood samples were collected from healthy women (n = 14) and men (n = 10) recruited prospectively from McMaster University (August 2014). Blood was collected from the cubital vein into plasma separator tubes containing five different anticoagulant systems [K2EDTA, Li-Hep, Li-Hep (gel), Na-Hep, Na-Hep (glass)], and placed on ice for transport to the lab for centrifugation. Plasma samples (n = 16) collected in K2EDTA tubes from women recruited to a previous study (April 2011 to December 2012) were used to determine the effect of multiple freeze–thaw cycles. Plasma BDNF was quantified using a commercially available ELISA kit. Plasma concentrations of BDNF were significantly affected by the type of plasma separator tube, storage-time, and number of freeze–thaw cycles. Storage temperature (− 20 vs. − 80 °C) did not significantly affect the quantity of BDNF measured as mean BDNF concentrations generally fell within our calculated acceptable change limit up to 6 months in the freezer. Our results suggest that for quantification of circulating BDNF blood collected in K2EDTA tubes and plasma stored up to 6 months at either − 20 or − 80 °C produces reproducible results that fall within an acceptable range. However, plasma samples stored beyond 6 months and repeated freeze–thaw cycles should be avoided.

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A combined score of clinical factors and serum proteins can predict time to recurrence in high grade serous ovarian cancer

Cited by 27 publications

References 22 publications

Multi-platform Affinity Proteomics Identify Proteins Linked to Metastasis and Immune Suppression in Ovarian Cancer Plasma

Multi-platform Affinity Proteomics Identify Proteins Linked to Metastasis and Immune Suppression in Ovarian Cancer Plasma

Advances in Aptamer-Based Biomarker Discovery

Factors affecting stability of plasma brain-derived neurotrophic factor

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